The reduction of the imide ester (+/-) trans-3-ethoxy-carbonyl-4-(4'-fluorophenyl)-N-methylpiperidine-2,6-dione (I) to the corresponding amino alcohol (+/-) trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine (II) is known. The chemical reduction of substrate I involves the conversion of the imide functionality into an amine and that of the ester group into an alcohol, resulting in amino alcohol II. This amino alcohol is a useful chemical intermediate in the synthesis of more complex organic compounds of medicinal value.
U.S. Pat. No. 4,902,801 describes the reduction of substrate I with lithium aluminum hydride (LAH) in a reaction concentration of approximately 0.33 Molar, with the solvent composition as 14% tetrahydrofuran and 86% toluene by volume. Yields reported for these specific conditions range from 65% to 75% isolated. In a similar example an increase in the percent tetrahydrofuran to 100%, that is, with no toluene present, still resulted in only a 65% isolated yield. Lithium aluminum hydride is a powerful but expensive reducing agent, making higher reaction yields and lower reagent cost critical for economic feasibility and wider industrial use.
Japanese Unexamined Patent H3-200762 to Maemoto et al. describes the reduction of the imide N-benzylmalic acid imide using sodium aluminum hydride with yields ranging from 52% to 63%. Reduction of imide (I) with sodium aluminum hydride alone gives similar yields of 50% or less.